Risk for leukemia after treatment for early stage breast cancer higher than reported

The risk of developing leukemia after radiation therapy or chemotherapy for early stage breast cancer remains very small, but it is twice as high as previously reported, according to results of a new, retrospective study published in the Journal of Clinical Oncology (2014; doi:10.1200/JCO.2013.54.6119).

The study team, led by researchers at the Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland, reviewed data on 20,063 patients with breast cancer treated at eight US cancer centers between 1998 and 2007 whose cancer recurrence and secondary cancers were recorded in a database kept by the National Comprehensive Cancer Network (NCCN).

In that group, 50 patients had developed some form of leukemia within 10 years after radiation therapy, chemotherapy, or a combination of the two. That translates to roughly a cumulative risk of 0.5%.

Data from earlier randomized clinical trials, which typically include just a few hundred patients, found that approximately 0.25% of breast cancer patients develop leukemia as a late effect of chemotherapy, said Judith Karp, MD, professor emerita of oncology at the Johns Hopkins University School of Medicine, who retired in 2013 as director of the Kimmel Cancer Center's Leukemia Program.

"The frequency of bone marrow cancers such as leukemia is small, there's no question about it," Karp said. "However, the cumulative risk over a decade is now shown to be twice as high as we thought it was, and that risk doesn't seem to slow down 5 years after treatment."

"Most medical oncologists have come to think that the risk is early and short-lived," said Karp. "So this was a little bit of a wake-up call that we are not seeing any plateau of that risk, and it is higher."

Antonio Wolff, MD, also at Johns Hopkins, said the study could help patients with early stage breast cancer and their physicians think more carefully about the use of chemotherapy for just-in-case reasons, especially when patients have a low risk of cancer recurrence.

"Our study provides useful information for physicians and patients to consider a potential downside of preventive or adjuvant chemotherapy in patients with very low risk of breast cancer recurrence," said Wolff. "It could be a false and dangerous security blanket to some patients by exposing them to a small risk of serious late effects with little or no real benefit from the treatment."

In recent years, oncologists have learned that postsurgical chemotherapy for breast cancer mostly benefits a small and select group of patients. NCCN clinical guidelines no longer recommend it for all patients with stage 1 breast cancers, defined as breast cancers 2 cm or smaller that have not spread to nearby lymph nodes.

Wolff said that each patient's treatment plan for early stage cancer could differ depending on a variety of factors, including the size of the tumors; whether the cancer has spread to the lymph nodes; and whether the tumor tests positive for certain breast cancer-related hormone and growth receptors, such as estrogen receptors (ERs) and human epidermal growth factor receptor 2 (HER2).